Left and Right Ventricular Hemodynamic Response After Transcatheter Mitral Valve Replacement.

Background: Transcatheter mitral valve replacement (TMVR) represents a novel treatment option for patients with mitral regurgitation (MR), but little is known about the hemodynamic impact of MR elimination following TMVR. We sought to investigate the hemodynamic impact of TMVR on left ventricular (LV) and right ventricular (RV) function using noninvasive pressure-volume loops. Methods: All consecutive patients undergoing TMVR with dedicated devices between May 2016 and August 2022 were enrolled. The end-diastolic and end-systolic pressure-volume relationships were estimated from 26 patients using single-beat echocardiographic measurements at baseline and after TMVR at discharge. RV function was assessed by RV-pulmonary artery (PA) coupling and RV fractional area change. One-year follow-up was available for 19 patients. The prognostic impact of calculated end-diastolic volume at an end-diastolic pressure of 20 mmHg (VPed20) reduction was assessed by Cox regression. Results: A total of 26 patients (77.0 years [interquartile range 73.9-80.1], N = 17 [65.4%] male) with successful TMVR were included (secondary MR [N = 21, 80.8%]; median LV ejection fraction was 37.0% [interquartile range 30.7-50.7]). At discharge, a decrease in VPed20 (p < 0.001) indicating leftward shift of end-diastolic pressure-volume relationship, and an increase of the end-systolic elastance slope (p = 0.007) were observed after TMVR. No changes were observed for RV-PA coupling (p = 0.19) and RV fractional area change (p = 0.22). At 1-year follow-up, LV contractility (end-systolic elastance) and RV-PA coupling remained stable. Vped20 reduction at discharge was significantly associated with 1-year all-cause mortality or heart failure hospitalization (hazard ratio 0.16, 95% CI 0.04-0.71, p = 0.016). Conclusions: Noninvasive assessment of pressure-volume loops demonstrated early LV reverse remodeling and improved LV contractility, while RV performance was preserved. These results indicate the potential prognostic impact of complete MR elimination after TMVR.

Evolution of Pulmonary Embolism Response Teams in the United States: A Review of the Literature.

Pulmonary embolism (PE) is a significant cause of cardiovascular mortality, with varying presentations and management challenges. Traditional treatment approaches often differ, particularly for submassive/intermediate-risk PEs, because of the lack of clear guidelines and comparative data on treatment efficacy. The introduction of pulmonary embolism response teams (PERTs) aims to standardize and improve outcomes in acute PE management through multidisciplinary collaboration. This review examines the conception, evolution, and operational mechanisms of PERTs while providing a critical analysis of their implementation and efficacy using retrospective trials and recent randomized trials. The study also explores the integration of advanced therapeutic devices and treatment protocols facilitated by PERTs. PERT programs have significantly influenced the management of both massive and submassive PEs, with notable improvements in clinical outcomes such as decreased mortality and reduced length of hospital stay. The utilization of advanced therapies, including catheter-directed thrombolysis and mechanical thrombectomy, has increased under PERT guidance. Evidence from various studies, including those from the National PERT Consortium, underscores the benefits of these multidisciplinary teams in managing complex PE cases, despite some studies showing no significant difference in mortality. PERT programs have demonstrated potentials to reduce morbidity and mortality, streamlining the use of healthcare resources and fostering a model of sustainable practice across medical centers. PERT program implementation appears to have improved PE treatment protocols and innovated advanced therapy options, which will be further refined as they are employed in clinical practice. The continued expansion of the capabilities of PERTs and the forthcoming results from ongoing randomized trials are expected to further define and optimize management protocols for acute PEs.

Impact of Intraprocedural Mitral Regurgitation and Gradient Following Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation.

BACKGROUND: The impact of intraprocedural results following transcatheter edge-to-edge repair (TEER) in primary mitral regurgitation (MR) is controversial. OBJECTIVES: This study sought to investigate the prognostic impact of intraprocedural residual mitral regurgitation (rMR) and mean mitral valve gradient (MPG) in patients with primary MR undergoing TEER. METHODS: The PRIME-MR (Outcomes of Patients Treated With Mitral Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation) registry included consecutive patients with primary MR undergoing TEER from 2008 to 2022 at 27 international sites. Clinical outcomes were assessed according to intraprocedural rMR and mean MPG. Patients were categorized according to rMR (optimal result: ≤1+, suboptimal result: ≥2+) and MPG (low gradient: ≤5 mm Hg, high gradient: > 5 mm Hg). The prognostic impact of rMR and MPG was evaluated in a Cox regression analysis. The primary endpoint was 2-year all-cause mortality or heart failure hospitalization. RESULTS: Intraprocedural rMR and mean MPG were available in 1,509 patients (median age = 82 years [Q1-Q3: 76.0-86.0 years], 55.1% male). Kaplan-Meier analysis according to rMR severity showed significant differences for the primary endpoint between rMR ≤1+ (29.1%), 2+ (41.7%), and ≥3+ (58.0%; P < 0.001), whereas there was no difference between patients with a low (32.4%) and high gradient (42.1%; P = 0.12). An optimal result/low gradient was achieved in most patients (n = 1,039). The worst outcomes were observed in patients with a suboptimal result/high gradient. After adjustment, rMR ≥2+ was independently linked to the primary endpoint (HR: 1.87; 95% CI: 1.32-2.65; P < 0.001), whereas MPG >5 mm Hg was not (HR: 0.78; 95% CI: 0.47-1.31; P = 0.35). CONCLUSIONS: Intraprocedural rMR but not MPG independently predicted clinical outcomes following TEER for primary MR. When performing TEER in primary MR, optimal MR reduction seems to outweigh the impact of high transvalvular gradients.

Routine postdilation after 23 mm Sapien 3 Ultra implantation in the aortic position.

BACKGROUND: Residual transprosthetic gradient (TG) after transcatheter aortic valve replacement (TAVR) with balloon-expandable valves (BEV) may be due to suboptimal valve expansion. AIMS: To compare hemodynamics after TAVR with small BEV according to postdilation strategy. METHODS: This observational, retrospective cohort study included 184 consecutive patients from a single center treated with 23 mm Sapien 3 Ultra (Edwards Lifesciences) BEV implantation in the aortic position and enrolled between January 2020 and April 2023. Patients treated with routine postdilation (RP, n = 73) were compared to patients treated according to local standard practice (SP, n = 111). Primary endpoint was 30-day mean TG. Secondary endpoints were incidence of 30-day prosthesis-patient mismatch (PPM), technical success and device success. RESULTS: Thirty-day mean TG was lower in RP versus SP (12.3 ± 4.6 mmHg vs. 14.1 ± 5.7 mmHg, p = 0.031), and incidence of PPM was less common with RP versus SP (47.3% vs. 71.0%, p = 0.006). Technical success (98.6% vs. 99.1%, p = 0.637) and device success (93.1% vs. 90.1%, p = 0.330) did not differ between groups. Differences in 30-day mean TG were driven by patients at normal flow (12.1 ± 4.0 mmHg vs. 15.0 ± 5.5 mmHg, p = 0.014), while no differences were evident among patients at low flow (12.5 ± 5.5 mmHg vs. 11.7 ± 5.5 mmHg, p = 0.644). RP decreased height and increased width of BEV, and a linear regression established that final BEV width could predict 30-day mean TG (r = -0.6654, p < 0.0001). CONCLUSIONS: RP after TAVR with small BEV was associated with more favorable forward-flow hemodynamics than SP.

Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium.

Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.

Incidence, Predictors, and Outcomes of Paravalvular Regurgitation After TAVR in Sievers Type 1 Bicuspid Aortic Valves.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR). OBJECTIVES: The aim of this study was to identify the incidence, predictors, and clinical outcomes of PVR after TAVR in Sievers type 1 BAV stenosis. METHODS: Consecutive patients with Sievers type 1 BAV stenosis undergoing TAVR with current-generation transcatheter heart valves (THVs) in 24 international centers were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAEs), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up. RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%)-mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were a larger virtual raphe ring perimeter (adjusted OR: 1.07; 95% CI: 1.02-1.13), severe annular or left ventricular outflow tract calcification (adjusted OR: 5.21; 95% CI: 1.45-18.77), a self-expanding valve (adjusted OR: 9.01; 95% CI: 2.09-38.86), and intentional supra-annular THV positioning (adjusted OR: 3.31; 95% CI: 1.04-10.54). At a median follow-up of 1.3 years (Q1-Q3: 0.5-2.4 years), moderate or severe PVR was associated with an increased risk of MAEs (adjusted HR: 2.52; 95% CI: 1.24-5.09). CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAEs during follow-up.

Short-Term Outcomes of ACURATE neo2.

Inferior outcomes with ACURATE neo, a self-expanding transcatheter heart valve (THV) for the treatment of severe aortic stenosis, were mainly driven by higher rates of moderate/severe paravalvular leak (PVL). To overcome this limitation, the next-generation ACURATE neo2 features a 60% larger external sealing skirt. Data on long-term performance are limited; however, clinical evidence suggests improved short-term performance which is comparable to contemporary THVs. This report reviews data on short-term clinical and echocardiographic outcomes of ACURATE neo2. A PubMed search yielded 13 studies, including 5 single arm and 8 nonrandomized comparative studies with other THVs which reported in-hospital or 30-day clinical and echocardiographic outcomes. In-hospital or 30-day all-cause mortality was ≤3.3%, which is comparable to other contemporary THVs. The rates of postprocedural ≧moderate PVL ranged 0.6%-4.7%. In multicenter propensity-matched analyses, neo2 significantly reduced the rate of ≧moderate PVL compared to neo (3.5% vs. 11.3%, p < 0.01), whereas rates were comparable to Evolut Pro/Pro+ (Neo2: 2.0% vs. Pro/Pro+: 3.1%, p = 0.28) and SAPIEN 3 Ultra (Neo2: 0.6% vs. Ultra: 1.1%, p = 0.72). The rate of permanent pacemaker implantation with neo2 was consistently low (3.3%-8.6%) except in one study, and in propensity-matched analyses were significantly lower than Evolut Pro/Pro+ (6.7% vs. 16.7%, p < 0.01), and comparable to SAPIEN 3 Ultra (8.1% vs. 10.3%, p = 0.29). In conclusion, ACURATE neo2 showed better short-term performance by considerably reducing PVL compared to its predecessor, with short-term clinical and echocardiographic outcomes comparable to contemporary THVs.

Interaction between risk factors, coronary calcium, and CCTA plaque characteristics in patients aged 18-45 years.

AIMS: The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. METHODS AND RESULTS: We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14-23.7) and OR 10.26 (3.36-31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05-6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67-4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08-4.86)]. CONCLUSION: In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group.

Real and In Silico Microgels Show Comparable Bulk Moduli Below and Above the Volume Phase Transition.

The compressibility of soft colloids influences their phase behavior and flow properties, especially in concentrated suspensions. Particle compressibility, which is proportional to the reciprocal of the bulk modulus K, is a key parameter for soft polymer-based particles that can be compressed in crowded environments. Here, microgels with different degrees of cross-linking, i.e., softness, are investigated below and above their volume phase transition temperature (VPTT). By combining molecular dynamics simulations with small-angle neutron scattering with contrast variation, a change in the particle bulk moduli of two orders of magnitude is observed. The degree of cross-linking has a significant impact on the bulk modulus of the swollen microgel, while above the VPTT the values of K are almost independent of the cross-linking density. The excellent agreement between experimental results and simulations also highlight that the model microgels from computer simulations possess both the internal architecture and the elastic properties of real polymeric networks. This paves the way to a systematic use of simulations to investigate the behavior of dense microgel suspensions below and above their VPTT.

Prediction of Mortality and Heart Failure Hospitalization After Transcatheter Tricuspid Valve Interventions: Validation of TRISCORE.

BACKGROUND: Data on the prognostic role of the TRI-SCORE in patients undergoing transcatheter tricuspid valve intervention (TTVI) are limited. OBJECTIVES: The aim of this study was to evaluate the performance of the TRI-SCORE in predicting outcomes of patients undergoing TTVI. METHODS: TriValve (Transcatheter Tricuspid Valve Therapies) is a large multicenter multinational registry including patients undergoing TTVI. The TRI-SCORE is a risk model recently proposed to predict in-hospital mortality after tricuspid valve surgery. The TriValve population was stratified based on the TRI-SCORE tertiles. The outcomes of interest were all-cause death and all-cause death or heart failure hospitalization. Procedural complications and changes in NYHA functional class were also reported. RESULTS: Among the 634 patients included, 223 patients (35.2%) had a TRI-SCORE between 0 and 5, 221 (34.8%) had 6 or 7, and 190 (30%) had ≥8 points. Postprocedural blood transfusion, acute kidney injury, new atrial fibrillation, and in-hospital mortality were more frequent in the highest TRI-SCORE tertile. Postprocedure length of stay increased with a TRI-SCORE increase. A TRI-SCORE ≥8 was associated with an increased risk of 30-day all-cause mortality and all-cause mortality and the composite endpoint assessed at a median follow-up of 186 days (OR: 3.00; 95% CI: 1.38-6.55; HR: 2.17; 95% CI: 1.78-4.13; HR: 2.08, 95% CI: 1.57-2.74, respectively) even after adjustment for procedural success and EuroSCORE II or Society of Thoracic Surgeons Predicted Risk of Mortality. The NYHA functional class improved across all TRI-SCORE values. CONCLUSIONS: In the TriValve registry, the TRI-SCORE has a suboptimal performance in predicting clinical outcomes. However, a TRISCORE ≥8 is associated with an increased risk of clinical events and a lack of prognostic benefit after successful TTVI.

Softness matters: effects of compression on the behavior of adsorbed microgels at interfaces.

Deformable colloids and macromolecules adsorb at interfaces as they decrease the interfacial energy between the two media. The deformability, or softness, of these particles plays a pivotal role in the properties of the interface. In this study, we employ a comprehensive in situ approach, combining neutron reflectometry with molecular dynamics simulations, to thoroughly examine the profound influence of softness on the structure of microgel Langmuir monolayers under compression. Lateral compression of both hard and soft microgel particle monolayers induces substantial structural alterations, leading to an amplified protrusion of the microgels into the aqueous phase. However, a critical distinction emerges: hard microgels are pushed away from the interface, in stark contrast to the soft ones, which remain firmly anchored to it. Concurrently, on the air-exposed side of the monolayer, lateral compression induces a flattening of the surface of the hard monolayer. This phenomenon is not observed for the soft particles as the monolayer is already extremely flat even in the absence of compression. These findings significantly advance our understanding of the key role of softness on both the equilibrium phase behavior of the monolayer and its effect when soft colloids are used as stabilizers of responsive interfaces and emulsions.

New approaches to triglyceride reduction: Is there any hope left?

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

Evolut PRO and SAPIEN ULTRA Performance in Small Aortic Annuli: The OPERA-TAVI Registry.

BACKGROUND: The performance of latest iteration transcatheter aortic valve replacement platforms in patients with small aortic anatomy remains underexplored. OBJECTIVES: The aim of this study was to evaluate effectiveness and performance between the self-expanding (SE) Evolut PRO and PRO+ and the balloon-expandable (BE) SAPIEN ULTRA in patients with small aortic annuli. METHODS: Data from the OPERA-TAVI (Comparative Analysis of Evolut PRO vs. SAPIEN 3 ULTRA Valves for Transfemoral Transcatheter Aortic Valve Implantation) registry were used, with 1:1 propensity score matching. Primary endpoints included 1-year effectiveness composite (all-cause mortality, disabling stroke, or heart failure hospitalization) and 30-day device-related (hemodynamic structural valve dysfunction and nonstructural valve dysfunction) outcomes. RESULTS: Among 3,516 patients, 251 matched pairs with aortic annular area <430 mm2 were assessed. The 1-year primary effectiveness outcome did not differ significantly between cohorts (SE 10.8% vs BE 11.2%; P = 0.91). The 30-day device-oriented composite outcome was more favorable in the Evolut PRO group (SE 4.8% vs BE 10.4%; P = 0.027). Notably, SE valve recipients showed higher rates of disabling stroke (SE 4.0% vs BE 0.0%; P < 0.01) and paravalvular leaks (mild or greater: SE 48.5% vs BE 18.6% [P < 0.001]; moderate: SE 4.5% vs BE 1.2% [P = 0.070]). The BE group had higher rates of prosthesis-patient mismatch (moderate or greater: SE 16.0% vs BE 47.1% [P < 0.001]; severe: SE 1.3% vs BE 5.7% [P = 0.197]) and more patients with residual mean gradients >20 mm Hg (SE 1.0% vs BE 13.5%; P < 0.001). CONCLUSIONS: In patients with small aortic annuli, transcatheter aortic valve replacement with latest iteration devices is safe. SE platforms are associated with more favorable device performance in terms of hemodynamic structural and nonstructural dysfunction. Randomized data are needed to validate these findings and guide informed device selection.

Association of cardiometabolic and vascular atherosclerosis phenotypes on non-contrast chest CT with incident heart failure in patients with severe hypercholesterolemia.

BACKGROUND: Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). OBJECTIVES: We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL. METHODS: We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization. RESULTS: We included 762 patients with median age 60 (53-68) years, 68% (n=520) female, and median LDL-C level of 203 (194-216) mg/dL. Patients were followed for 4.7 (interquartile range 2.75-6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p<0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF. CONCLUSIONS: In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD, and EAT were not.

Sex-Related Outcomes of Transcatheter Aortic Valve Implantation With Self-Expanding or Balloon-Expandable Valves: Insights from the OPERA-TAVI Registry.

Evidence regarding gender-related differences in response to transcatheter aortic valve implantation according to the valve type is lacking. This study aimed to evaluate the impact of gender on the treatment effect of Evolut PRO/PRO+ (PRO) or SAPIEN 3 Ultra (ULTRA) devices on clinical outcomes. The Comparative Analysis of Evolut PRO vs SAPIEN 3 Ultra Valves for Transfemoral Transcatheter Aortic Valve Implantation (OPERA-TAVI) is a multicenter, multinational registry including patients who underwent the latest-iteration PRO or ULTRA implantation. Overall, 1,174 of 1,897 patients were matched based on valve type and compared according to gender, whereas 470 men and 630 women were matched and compared according to valve type. The 30-day and 1-year outcomes were evaluated. In the PRO and ULTRA groups, men had a higher co-morbidity burden, whereas women had smaller aortic root. The 30-day (device success [DS], early safety outcome, permanent pacemaker implantation, patient-prosthesis mismatch, paravalvular regurgitation, bleedings, vascular complications, and all-cause death) and 1-year outcomes (all-cause death, stroke, and heart failure hospitalization) did not differ according to gender in both valve groups. However, the male gender decreased the likelihood of 30-day DS with ULTRA versus PRO (p for interaction = 0.047). A higher risk of 30-day permanent pacemaker implantation and 1-year stroke and a lower risk of patient-prosthesis mismatch was observed in PRO versus ULTRA, regardless of gender. In conclusion, gender did not modify the treatment effect of PRO versus ULTRA on clinical outcomes, except for 30-day DS, which was decreased in men (vs women) who received ULTRA (vs PRO).